Performance of p16/Ki67 immunostaining, HPV E6/E7 mRNA testing, and HPV DNA assay to detect high-grade cervical dysplasia in women with ASCUS

BMC Cancer. 2019 Mar 27;19(1):271. doi: 10.1186/s12885-019-5492-9.

Abstract

Background: Atypical squamous cell of undetermined significance (ASCUS) is a common cervical cytological diagnosis. At present, HPV DNA assay is used to triage these patients, but its lower specificity brings a series of problems. The purpose of this study was to evaluated the value of p16/Ki67 immunostaining, HPV E6/E7 mRNA testing in triaging women with ASCUS by comparing HPV DNA assay.

Methods: Liquid based cytology specimens were collected from 300 patients. P16/Ki67 immunocytochemistry using the CINtec® Plus Kit and HPV E6/E7 mRNA testing by QuantiVirus®HPV E6/E7 mRNA assay used the same cytology sample. Detection rates of each test were evaluated against histopathology.

Results: All assays yielded a high sensitivity for the detection of CIN3+ (100% (86.7-100) for HPV DNA assay, 88.0% (70.0-95.8) for HPV E6/E7 mRNA testing and 100% (86.7-100) for p16/Ki67 immunocytochemistry) and CIN2+ (98.2% (90.2-99.7) for HPV DNA assay, 87.0% (75.6-93.6) for HPV E6/E7 mRNA testing, 98.2% (90.2-99.7) for p16/Ki67 immunocytochemistry). The specificity to detect high grade dysplasia was highest for p16/Ki67 immunocytochemistry (74.2% (68.7-79.0) in CIN3+ and 82.5% (77.3-86.8) in CIN2+), followed by HPV E6/E7 mRNA testing (39.6% (34.0-45.5) in CIN3+ and 42.7% (36.7-48.9) in CIN2+) and HPV DNA assay (16.0% (12.1-20.8) in CIN3+ and 17.5% (13.2-22.7) in CIN2+).

Conclusions: p16/Ki67 immunostaining and HPV E6/E7 mRNA testing, especially the former, may be promising tools in triage of ASCUS.

Keywords: ASCUS; CIN; E6/E7; HPV; mRNA; p16/Ki67.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Atypical Squamous Cells of the Cervix / metabolism
  • Atypical Squamous Cells of the Cervix / virology*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA, Viral / genetics
  • Early Diagnosis
  • Female
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Middle Aged
  • Oncogene Proteins, Viral / genetics*
  • Papillomaviridae / genetics*
  • Papillomaviridae / metabolism
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / metabolism
  • Papillomavirus Infections / virology
  • Sensitivity and Specificity
  • Triage
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / virology
  • Young Adult

Substances

  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Viral
  • Ki-67 Antigen
  • Oncogene Proteins, Viral